Advances in modern medicine have dramatically enhanced life expectancy for youth born with spina bifida. A family-centered approach to research and service provision is thought to be essential to promote positive psychosocial outcomes for all members. However, there is a paucity of data on adjustment outcomes for siblings, and available research has primarily focused on the detection of psychopathologies rather than the identification of competencies and strengths. Yet, developing effective prevention and intervention programs necessitates understanding factors heightening vulnerability to adjustment difficulties as well as those mechanisms bufferring risk. The present cross-sectional mixed method study, based in a risk and resilience perspective of human behavior, tests an ecological model of adjustment for siblings recruited from five culturally and geographically distinct locations. The research will uniquely contribute to the family health literature by investigating whether stress appraisal, sibling relationship characteristics, satisfaction with family functioning, and peer social support are protective factors for the psychological and behavioral adjustment of adolescent siblings of youth with spina bifida.